1. Field of the Invention
The presently disclosed and claimed inventive concept(s) is related in general to compositions for inhibition of ribosomal RNA synthesis, and methods of producing and using same.
2. Description of the Background
In 1934 W. C. MacCarthy published an article describing the irregular shapes of the nucleoli of cancer cells. This manuscript was the first to formally demonstrate that the nucleolus, the site of ribosomal RNA synthesis, was unusual in cancer cells. Subsequent studies have demonstrated highly elevated rates of rRNA synthesis in tumors and elevated rates in hypertrophic tissues. Hence, there has been a long-term goal to discover a method to specifically inhibit rDNA transcription in tumor cells.
Deregulated ribosomal RNA synthesis is associated with cancer cell proliferation. RNA polymerase I (Pol I), the multiprotein complex that synthesizes rRNA, is activated in most cancers. Thus, it is possible that selective inhibitors of Pol I and the transcription process may offer a general therapeutic strategy to inhibit cancer cell proliferation. Currently there are only two mechanisms that target transcription by RNA polymerase I in cancer cells. The first drug is actinomycin D, which has broad effects on cellular physiology. The second drug is CX-5461; this small molecule inhibitor of rDNA transcription is believed to act by blocking rDNA transcription initiation relative to its effects on transcription by RNA polymerase II, DNA replication and protein synthesis. However, its precise mechanism of action is not defined. Interestingly, CX-5461 does not induce apoptosis, which some have claimed to be the outcome of inhibiting rDNA transcription.
There exists a need in the art for new and improved compositions for inhibition of RNA Pol I, as well as methods of producing and using same. The presently disclosed and claimed inventive concept(s) is directed to said compositions and methods, which overcome the disadvantages and defects of the prior art.